Deracemization of Racemic Amines to Enantiopure (R)‐ and (S)‐amines by Biocatalytic Cascade Employing ω‐Transaminase and Amine Dehydrogenase

Abstract

A one‐pot deracemization strategy for α‐chiral amines is reported involving an enantioselective deamination to the corresponding ketone followed by a stereoselective amination by enantiocomplementary biocatalysts. Notably, this cascade employing a ω‐transaminase and amine dehydrogenase enabled the access to both (R)‐and (S)‐amine products, just by controlling the directions of the reactions catalyzed by them. A wide range of (R)‐and (S)‐amines was obtained with excellent conversions (>80 %) and enantiomeric excess (>99 % ee). Finally, preparative scale syntheses led to obtain enantiopure (R)‐ and (S)‐13 with the isolated yields of 53 and 75 %, respectively.

Deracemisation Processes Employing Organocatalysis and Enzyme Catalysis

“…In 2019 the deracemisation of a set of racemic amines to the corresponding ( R )‐ or ( S )‐enantiomers by combining ω‐TAs and amine dehydrogenases(AmDHs) in a biocatalytic cascade process was described . In order to obtain the ( R )‐amines, the initial step consists in the selective deamination of racemic amines catalysed by different ( S )‐selective ω‐TAs, as shown in Scheme .…”

“… Deracemisation of racemic amines to the ( R )‐enantiomers by combining ω‐TAs and amine dehydrogenases (AmDHs) …”

Kinetic Resolution of Racemic Primary Amines Using Geobacillus stearothermophilus Amine Dehydrogenase Variant

“…Complementary strategies include deracemisation cascades in which stereocomplementary AmDH and ωTA, or vice versa, perform stereoselective oxidative deamination followed by stereoselective reductive amination …”

Kinetic Resolution of Racemic Amines to Enantiopure (S)-amines by a Biocatalytic Cascade Employing Amine Dehydrogenase and Alanine Dehydrogenase

“…The genes encoding these AmDHs were cloned in pET-24ma vector and transformed in E. coli BL21 (DE3). Following the induction of transformants by IPTG, the His-tagged proteins were purified as previously reported [33].…”

“…Since the stability and activity of the biocatalysts are dependent on the pH, they can critically affect the overall outcome of the biocatalytic reaction. Especially for reactions catalyzed by the enzymatic cascades, wherein each constituent enzyme exhibits different optimum pH, the pH of the reaction should be carefully determined so that activity of the enzymes is not severely compromised [10,32,33]. Thus, the effect of varying pH on the activities of AmDHs and AlaDH was evaluated (Figure 3).…”